ANTIAPOPTOTIC EFFECT OF TAURINE AGAINST NMDA-INDUCED RETINAL EXCITOTOXICITY IN RATS

Research output: Contribution to journalArticle

Abstract

Objective: N-methyl-D-aspartate (NMDA) excitotoxicity has been proposed to mediate apoptosis of retinal ganglion cells (RGCs) in glaucoma. Taurine (TAU) has been shown to have neuroprotective properties, thus we examined anti-apoptotic effect of TAU against retinal damage after NMDA exposure. Methodology: Sprague-Dawley rats were divided into 5 groups of 33 each. Group 1 was administered intravitreally with PBS and group 2 was similarly injected with NMDA (160 nmol). Groups 3, 4 and 5 were injected with TAU (320 nmol) 24 hours before (pre-treatment), in combination (co-treatment) and 24 hours after (post-treatment) NMDA exposure respectively. Seven days after injection, rats were sacrificed; eyes were enucleated, fixed and processed for morphometric analysis, TUNEL and caspase-3 staining. Optic nerve morphology assessment was done using toluidine blue staining. The estimation of BDNF, pro/anti-apoptotic factors (Bax/Bcl-2) and caspase-3 activity in retina was done using ELISA technique. Results: Severe degenerative changes were observed in retinae after intravitreal NMDA exposure. The retinal morphology in the TAU pre-treated group appeared more similar to the control retinae and demonstrated a higher number of nuclei than the NMDA group both per 100 μm length (by 1.5-fold, p < 0.001) and per 100 μm2 area (by 1.41-fold, p < 0.05) of the GCL. After NMDA exposure, visible axonal swelling was observed in optic nerve sections. In comparison with the changes observed in the NMDA treated group, the TAU treated group showed fewer prominent changes; axonal swelling was less frequent and less marked. Additionally, no marked glial cell changes were observed in the TAU-pretreated group. All TAU treated groups, particularly the pre-treated group, showed a significant decrease in the NMDA-induced optic nerve damage, with a 50% reduction (p < 0.001) in the mean grading compared to NMDA group. For the same, there was 25% decrease in co- and post-treatment groups, as compared with the NMDA group. Pre-treatment with TAU abolished apoptotic response to NMDA as indicated by decrease in the number of TUNEL- and caspase-3-positive cells. TAU pre-treatment also increased the Bcl-2 level (by 2.80-fold, p < 0.001) and decreased the level of Bax (by 34%, p < 0.01), and activity of caspase-3 (by 36%, p < 0.001) compared to NMDA group. In conclusion: our study revealed that pre-treatment with TAU prevents NMDA-induced retinal cell apoptosis more effectively than co- and post-treatment with TAU.

LanguageEnglish
Pages62-71
Number of pages10
JournalNeuroToxicology
Volume70
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Taurine
Brain-Derived Neurotrophic Factor
N-Methylaspartate
Glaucoma
Retina
Rats
Caspase 3
Optic Nerve
Optics
In Situ Nick-End Labeling
Neuroprotection
Therapeutics
Swelling
Cells
Apoptosis
Staining and Labeling
Tolonium Chloride
Retinal Ganglion Cells
Neuroglia
Sprague Dawley Rats

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Toxicology

Cite this

ANTIAPOPTOTIC EFFECT OF TAURINE AGAINST NMDA-INDUCED RETINAL EXCITOTOXICITY IN RATS. / Lambuk, Lidawani; Iezhitsa, Igor Nikolayevich; Agarwal, Renu; Bakar, Nor Salmah; Agarwal, Puneet; Ismail, Nafeeza Mohd.

In: NeuroToxicology, Vol. 70, 01.01.2019, p. 62-71.

Research output: Contribution to journalArticle

@article{2544459291424a64be18feb0bcc9ee51,
title = "ANTIAPOPTOTIC EFFECT OF TAURINE AGAINST NMDA-INDUCED RETINAL EXCITOTOXICITY IN RATS",
abstract = "Objective: N-methyl-D-aspartate (NMDA) excitotoxicity has been proposed to mediate apoptosis of retinal ganglion cells (RGCs) in glaucoma. Taurine (TAU) has been shown to have neuroprotective properties, thus we examined anti-apoptotic effect of TAU against retinal damage after NMDA exposure. Methodology: Sprague-Dawley rats were divided into 5 groups of 33 each. Group 1 was administered intravitreally with PBS and group 2 was similarly injected with NMDA (160 nmol). Groups 3, 4 and 5 were injected with TAU (320 nmol) 24 hours before (pre-treatment), in combination (co-treatment) and 24 hours after (post-treatment) NMDA exposure respectively. Seven days after injection, rats were sacrificed; eyes were enucleated, fixed and processed for morphometric analysis, TUNEL and caspase-3 staining. Optic nerve morphology assessment was done using toluidine blue staining. The estimation of BDNF, pro/anti-apoptotic factors (Bax/Bcl-2) and caspase-3 activity in retina was done using ELISA technique. Results: Severe degenerative changes were observed in retinae after intravitreal NMDA exposure. The retinal morphology in the TAU pre-treated group appeared more similar to the control retinae and demonstrated a higher number of nuclei than the NMDA group both per 100 μm length (by 1.5-fold, p < 0.001) and per 100 μm2 area (by 1.41-fold, p < 0.05) of the GCL. After NMDA exposure, visible axonal swelling was observed in optic nerve sections. In comparison with the changes observed in the NMDA treated group, the TAU treated group showed fewer prominent changes; axonal swelling was less frequent and less marked. Additionally, no marked glial cell changes were observed in the TAU-pretreated group. All TAU treated groups, particularly the pre-treated group, showed a significant decrease in the NMDA-induced optic nerve damage, with a 50{\%} reduction (p < 0.001) in the mean grading compared to NMDA group. For the same, there was 25{\%} decrease in co- and post-treatment groups, as compared with the NMDA group. Pre-treatment with TAU abolished apoptotic response to NMDA as indicated by decrease in the number of TUNEL- and caspase-3-positive cells. TAU pre-treatment also increased the Bcl-2 level (by 2.80-fold, p < 0.001) and decreased the level of Bax (by 34{\%}, p < 0.01), and activity of caspase-3 (by 36{\%}, p < 0.001) compared to NMDA group. In conclusion: our study revealed that pre-treatment with TAU prevents NMDA-induced retinal cell apoptosis more effectively than co- and post-treatment with TAU.",
author = "Lidawani Lambuk and Iezhitsa, {Igor Nikolayevich} and Renu Agarwal and Bakar, {Nor Salmah} and Puneet Agarwal and Ismail, {Nafeeza Mohd}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.neuro.2018.10.009",
language = "English",
volume = "70",
pages = "62--71",
journal = "NeuroToxicology",
issn = "0161-813X",
publisher = "Elsevier",

}

TY - JOUR

T1 - ANTIAPOPTOTIC EFFECT OF TAURINE AGAINST NMDA-INDUCED RETINAL EXCITOTOXICITY IN RATS

AU - Lambuk, Lidawani

AU - Iezhitsa, Igor Nikolayevich

AU - Agarwal, Renu

AU - Bakar, Nor Salmah

AU - Agarwal, Puneet

AU - Ismail, Nafeeza Mohd

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: N-methyl-D-aspartate (NMDA) excitotoxicity has been proposed to mediate apoptosis of retinal ganglion cells (RGCs) in glaucoma. Taurine (TAU) has been shown to have neuroprotective properties, thus we examined anti-apoptotic effect of TAU against retinal damage after NMDA exposure. Methodology: Sprague-Dawley rats were divided into 5 groups of 33 each. Group 1 was administered intravitreally with PBS and group 2 was similarly injected with NMDA (160 nmol). Groups 3, 4 and 5 were injected with TAU (320 nmol) 24 hours before (pre-treatment), in combination (co-treatment) and 24 hours after (post-treatment) NMDA exposure respectively. Seven days after injection, rats were sacrificed; eyes were enucleated, fixed and processed for morphometric analysis, TUNEL and caspase-3 staining. Optic nerve morphology assessment was done using toluidine blue staining. The estimation of BDNF, pro/anti-apoptotic factors (Bax/Bcl-2) and caspase-3 activity in retina was done using ELISA technique. Results: Severe degenerative changes were observed in retinae after intravitreal NMDA exposure. The retinal morphology in the TAU pre-treated group appeared more similar to the control retinae and demonstrated a higher number of nuclei than the NMDA group both per 100 μm length (by 1.5-fold, p < 0.001) and per 100 μm2 area (by 1.41-fold, p < 0.05) of the GCL. After NMDA exposure, visible axonal swelling was observed in optic nerve sections. In comparison with the changes observed in the NMDA treated group, the TAU treated group showed fewer prominent changes; axonal swelling was less frequent and less marked. Additionally, no marked glial cell changes were observed in the TAU-pretreated group. All TAU treated groups, particularly the pre-treated group, showed a significant decrease in the NMDA-induced optic nerve damage, with a 50% reduction (p < 0.001) in the mean grading compared to NMDA group. For the same, there was 25% decrease in co- and post-treatment groups, as compared with the NMDA group. Pre-treatment with TAU abolished apoptotic response to NMDA as indicated by decrease in the number of TUNEL- and caspase-3-positive cells. TAU pre-treatment also increased the Bcl-2 level (by 2.80-fold, p < 0.001) and decreased the level of Bax (by 34%, p < 0.01), and activity of caspase-3 (by 36%, p < 0.001) compared to NMDA group. In conclusion: our study revealed that pre-treatment with TAU prevents NMDA-induced retinal cell apoptosis more effectively than co- and post-treatment with TAU.

AB - Objective: N-methyl-D-aspartate (NMDA) excitotoxicity has been proposed to mediate apoptosis of retinal ganglion cells (RGCs) in glaucoma. Taurine (TAU) has been shown to have neuroprotective properties, thus we examined anti-apoptotic effect of TAU against retinal damage after NMDA exposure. Methodology: Sprague-Dawley rats were divided into 5 groups of 33 each. Group 1 was administered intravitreally with PBS and group 2 was similarly injected with NMDA (160 nmol). Groups 3, 4 and 5 were injected with TAU (320 nmol) 24 hours before (pre-treatment), in combination (co-treatment) and 24 hours after (post-treatment) NMDA exposure respectively. Seven days after injection, rats were sacrificed; eyes were enucleated, fixed and processed for morphometric analysis, TUNEL and caspase-3 staining. Optic nerve morphology assessment was done using toluidine blue staining. The estimation of BDNF, pro/anti-apoptotic factors (Bax/Bcl-2) and caspase-3 activity in retina was done using ELISA technique. Results: Severe degenerative changes were observed in retinae after intravitreal NMDA exposure. The retinal morphology in the TAU pre-treated group appeared more similar to the control retinae and demonstrated a higher number of nuclei than the NMDA group both per 100 μm length (by 1.5-fold, p < 0.001) and per 100 μm2 area (by 1.41-fold, p < 0.05) of the GCL. After NMDA exposure, visible axonal swelling was observed in optic nerve sections. In comparison with the changes observed in the NMDA treated group, the TAU treated group showed fewer prominent changes; axonal swelling was less frequent and less marked. Additionally, no marked glial cell changes were observed in the TAU-pretreated group. All TAU treated groups, particularly the pre-treated group, showed a significant decrease in the NMDA-induced optic nerve damage, with a 50% reduction (p < 0.001) in the mean grading compared to NMDA group. For the same, there was 25% decrease in co- and post-treatment groups, as compared with the NMDA group. Pre-treatment with TAU abolished apoptotic response to NMDA as indicated by decrease in the number of TUNEL- and caspase-3-positive cells. TAU pre-treatment also increased the Bcl-2 level (by 2.80-fold, p < 0.001) and decreased the level of Bax (by 34%, p < 0.01), and activity of caspase-3 (by 36%, p < 0.001) compared to NMDA group. In conclusion: our study revealed that pre-treatment with TAU prevents NMDA-induced retinal cell apoptosis more effectively than co- and post-treatment with TAU.

UR - http://www.scopus.com/inward/record.url?scp=85056480104&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056480104&partnerID=8YFLogxK

U2 - 10.1016/j.neuro.2018.10.009

DO - 10.1016/j.neuro.2018.10.009

M3 - Article

VL - 70

SP - 62

EP - 71

JO - NeuroToxicology

T2 - NeuroToxicology

JF - NeuroToxicology

SN - 0161-813X

ER -